PKU Flashcards
Children w/ untreated PKU rarely reach IQ over __
50
Urine in people w/ PKU
. Metabolites make urine musty
. Phenylpyruvate found in urine
Neonatal screening of PKU
. Neonates initially have no signs or symptoms
. Screening mandatory in every state
. Done at 49 hours of age because parent clears excess Phe in utero
. Guthrie screening test identifies PKU in babies
Prenatal diagnosis of PKU
. Gene for PAH located on chromosome 13
. Contains 13 Exons separated by introns
. DNA analysis can be done to identify markers
. Restriction fragment length polymorphism (RFLP) used to carry out prenatal diagnosis
PKU treatment
. Must start in first 7-10 days to prevent intellectual disability
. Lifelong restriction of dietary Phe
. Synthetic amino acid preparations used
. Can supplement w/ some natural foods (fruits, veggies, some cereals)
. Tyr can’t be synthesized from Phe and must be supplied in diet
Function of dihydropteridine reductase
Converts BH2 to BH4
. Enzyme can be mutated causing PKU
. BH4 also needed for Tyr hydroxylase that catalyze rxns for serotonin and catecholamine synthesis that is affected again
High Phe effects on transport in brain
. High concentrations of Phe inhibit transport of Tyr and Trp into brain and inc. Phe to brain
. Inc. possibility of neurotransmitter dysfunction
. Abnormal brain myelination and deficiency of brain large neutral AA can play role in impaired cognition
Skeletal changes seen in PKU
. Small head
. Short stature
. Flat feet
Movement symptoms in PKU
. Eczema
. Tremors
. Jerking of arms or legs
. Unusual hand posturing
Current method for PKU screening
. Mass spec
. Allows analysis for multiple diseases
. Positive tests followed up w/ specific tests
Normal limits of Phe in people w/ PKU
2 and 6 mg/dl
Challenges of dietary control
. Bland die
. Social implications: can’t eat most foods that peers consume
. Economic and health care systems barriers: cost of low Phe can be high expiate it being considered a medical food
Synthetic BH4
. Causes residual PAH enzyme activity to inc. to reduce blood Phe levels
. Effective in dec. blood Phe in some people w/ PKU
. Only effective in people that have some normal PAH activity
Phe uptake blockers
. Large neutral amino acids (LNAA’s) block Phe uptake through digestive tract
Maternal PKU
. Mom’s have PKU
. High level Phe cause microcephaly, intellectual disability, and heart abnormalities in fetus
. Can cause miscarriage, growth retardation, craniofacial dysmorphic features
. Take effect in 1st trimester
. Need strict control over diet before conception and continued throughout pregnancy
